In resource-limited settings progress in scaling up services for prevention of mother-to-child transmission of HIV (PMTCT) continues to lag behind the rest of the world. Nigeria has one of the highest burdens of mother-to-child transmission of HIV in the world. The elimination of mother-to-child transmission of HIV in Nigeria will require innovative methods of PMTCT service delivery at the lowest level of the health care system, consistent with appropriate, feasible and effective care. The goal of this study is to implement and evaluate the impact of a family- focused integrated PMTCT package comprising task shifting, point-of-care CD4 testing, and a prominent role for influential family members (particularly male partners) in rural primary health centers in Nigeria. The specific aims of this study are: (1) To evaluate whether implementation of the integrated PMTCT package in primary level antenatal clinics increases the proportion of eligible pregnant women who initiate antiretroviral medications for the purposes of PMTCT; (2) To determine whether implementation of the PMTCT package improves postpartum retention of mother-infant pairs at 6 weeks; and (3) Conduct a cost-effectiveness analysis of the impact of this novel PMTCT intervention compared to the existing standard-of-care referral model. We have assembled a strong team of Nigerian and American scientists with expertise in PMTCT cluster randomized trials, adherence and retention in care, HIV risk behavior, cART outcomes, and cost-effectiveness analysis of HIV programs. We include a rigorous study design and triangulation of data collection methods (quantitative outcomes, cost effectiveness analysis, qualitative surveys) that will yield valuable complimentary data. We will build on existing in- country PEPFAR infrastructure, established partnerships, and strong local presence, thereby increasing the likelihood of successful study implementation. PUBLIC HEALTH RELEVANCE: This innovative approach to scaling up PMTCT service provision, if proven feasible and effective, will be adopted in PEPFAR programs to accelerate progress toward eliminating mother-to-child transmission of HIV and helping women with HIV infection live long, healthy lives. The purpose of this R01 proposal is to evaluate the impact and cost-effectiveness of a family-focused integrated prevention of mother-to-child transmission of HIV (PMTCT) package comprising task shifting of PMTCT services (including antiretroviral therapy) to lower-cadre workers, adoption of point-of-care CD4 testing, and a prominent role for influential family members of HIV-infected mothers in rural Nigeria. This innovative approach to scaling up PMTCT service provision, if proven feasible and effective, will be adopted in PEPFAR programs to accelerate progress toward eliminating mother-to-child transmission of HIV and helping women with HIV infection live long, healthy lives.